Bottom Line:
Additionally, mRNA expression of lipases was determined in biopsies from SCAAT.Furthermore, mRNA expression of lipases was significantly decreased in the SCAAT of FDR subjects.Physical inactivity per se is not more deleterious in FDR subjects as compared with CON subjects with respect to derangements in AT metabolism.

Objective: Physical inactivity is a risk factor for type 2 diabetes and may be more detrimental in first-degree relative (FDR) subjects, unmasking underlying defects of metabolism. Using a positive family history of type 2 diabetes as a marker of increased genetic risk, the aim of this study was to investigate the impact of physical inactivity on adipose tissue (AT) metabolism in FDR subjects.

Research design and methods: A total of 13 FDR and 20 control (CON) subjects participated in the study. All were studied before and after 10 days of bed rest using the glucose clamp technique combined with measurements of glucose uptake, lipolysis, and lactate release from subcutaneous abdominal (SCAAT) and femoral (SCFAT) adipose tissue by the microdialysis technique. Additionally, mRNA expression of lipases was determined in biopsies from SCAAT.

Results: Before bed rest, the FDR subjects revealed significantly increased glucose uptake in SCAAT. Furthermore, mRNA expression of lipases was significantly decreased in the SCAAT of FDR subjects. Bed rest significantly decreased lipolysis and tended to increase glucose uptake in the SCFAT of both CON and FDR subjects. In response to bed rest, SCAAT glucose uptake significantly increased in CON subjects but not in FDR subjects.

Conclusions: FDR subjects exhibit an abnormal AT metabolism including increased glucose uptake prior to bed rest. However, the differences between FDR and CON subjects in AT metabolism were attenuated during bed rest due to relatively more adverse changes in CON subjects compared with FDR subjects. Physical inactivity per se is not more deleterious in FDR subjects as compared with CON subjects with respect to derangements in AT metabolism.

Figure 1: SCAAT and SCFAT glucose uptake in the basal state (no pattern) and the insulin-stimulated state (patterned) before (gray) and after (black) bed rest (BR) in CON and FDR of type 2 diabetic subjects. *Basal (P = 0.005) and insulin-stimulated state (P = 0.02) before bed rest, CON vs. FDR. **Basal (P = 0.01) and insulin-stimulated state (P = 0.02) before vs. after bed rest in CON.

Mentions:
The figures presented (Figs. 1–3) are absolute means, while the differences and CIs described in the results section are from the linear mixed model. If data were not normally distributed or homogeneous as assessed by residual plots of each dependent variable, log transformation data were used and significant effects described as relative (%) differences. We evaluated the effect of groups (CON and FDR), the effect of bed rest (before vs. after), and time (baseline or insulin-stimulated) and tested an eventual differential effect of bed rest between FDR and CON subjects by including interaction between groups and bed rest and the marginal effects in the model. Threshold for significance was P ≤ 0.05. The Bonferroni corrected P value that is equivalent to an uncorrected P value of 0.05 in the present study is P = 0.0028, although this is likely overly conservative. However in the interpretation of the results, the risks of type I errors are acknowledged. Data are presented as absolute means ± SE (figures) or differences and CI.

Figure 1: SCAAT and SCFAT glucose uptake in the basal state (no pattern) and the insulin-stimulated state (patterned) before (gray) and after (black) bed rest (BR) in CON and FDR of type 2 diabetic subjects. *Basal (P = 0.005) and insulin-stimulated state (P = 0.02) before bed rest, CON vs. FDR. **Basal (P = 0.01) and insulin-stimulated state (P = 0.02) before vs. after bed rest in CON.

Mentions:
The figures presented (Figs. 1–3) are absolute means, while the differences and CIs described in the results section are from the linear mixed model. If data were not normally distributed or homogeneous as assessed by residual plots of each dependent variable, log transformation data were used and significant effects described as relative (%) differences. We evaluated the effect of groups (CON and FDR), the effect of bed rest (before vs. after), and time (baseline or insulin-stimulated) and tested an eventual differential effect of bed rest between FDR and CON subjects by including interaction between groups and bed rest and the marginal effects in the model. Threshold for significance was P ≤ 0.05. The Bonferroni corrected P value that is equivalent to an uncorrected P value of 0.05 in the present study is P = 0.0028, although this is likely overly conservative. However in the interpretation of the results, the risks of type I errors are acknowledged. Data are presented as absolute means ± SE (figures) or differences and CI.

Bottom Line:
Additionally, mRNA expression of lipases was determined in biopsies from SCAAT.Furthermore, mRNA expression of lipases was significantly decreased in the SCAAT of FDR subjects.Physical inactivity per se is not more deleterious in FDR subjects as compared with CON subjects with respect to derangements in AT metabolism.

Objective: Physical inactivity is a risk factor for type 2 diabetes and may be more detrimental in first-degree relative (FDR) subjects, unmasking underlying defects of metabolism. Using a positive family history of type 2 diabetes as a marker of increased genetic risk, the aim of this study was to investigate the impact of physical inactivity on adipose tissue (AT) metabolism in FDR subjects.

Research design and methods: A total of 13 FDR and 20 control (CON) subjects participated in the study. All were studied before and after 10 days of bed rest using the glucose clamp technique combined with measurements of glucose uptake, lipolysis, and lactate release from subcutaneous abdominal (SCAAT) and femoral (SCFAT) adipose tissue by the microdialysis technique. Additionally, mRNA expression of lipases was determined in biopsies from SCAAT.

Results: Before bed rest, the FDR subjects revealed significantly increased glucose uptake in SCAAT. Furthermore, mRNA expression of lipases was significantly decreased in the SCAAT of FDR subjects. Bed rest significantly decreased lipolysis and tended to increase glucose uptake in the SCFAT of both CON and FDR subjects. In response to bed rest, SCAAT glucose uptake significantly increased in CON subjects but not in FDR subjects.

Conclusions: FDR subjects exhibit an abnormal AT metabolism including increased glucose uptake prior to bed rest. However, the differences between FDR and CON subjects in AT metabolism were attenuated during bed rest due to relatively more adverse changes in CON subjects compared with FDR subjects. Physical inactivity per se is not more deleterious in FDR subjects as compared with CON subjects with respect to derangements in AT metabolism.